What Our Genome Says about the Origins of the … Single Nucleotide Polymorphism ‡ Illustrations: Saori Yasutomi Naruya Saitou, Genomu to Shinka – Genomu kara Tachinoboru Seimei

Naruya Saitou National Institute of Genetics

The figures, photos and moving images with ‡marks attached belong to their copyright holders. Reusing or reproducing them is prohibited unless permission is obtained directly from such copyright holders.

‡

Naruya Saitou, DNA kara Mita Nihonjin (The Japanese viewed from DNA), Chikuma Shinsho, 2005

Global Focus on Knowledge Lecture Series Puzzling Out the System of Life

What Our Genome Says about the Origins of the Japanese

May 1, Year 9 of the Scientific Era Bldg 18 Lecture Hall, Komaba Campus, The Univ. of Tokyo

Who Is "Japanese"?

• People with Japanese nationality? • People who speak Japanese? • People who look Japanese? • People who live in Japan?

Periods of Human History in the Japanese Islands

‡ Naruya Saitou, E de Wakaru Jinrui no Shinka(Evolution of the Human Race which is Understood with Pictures), Koudan Sha, 2009. Illustrations: Saori Yasutomi

The New View

B.C. A.D.

The Jyomon Era Late period Final period

The Yayoi Era

The Jyomon Era

Final period

The Yayoi Era The Kofun Era

The Kofun Era

Late period

The Old View

Periods of Human History in the Japanese Islands

‡ Naruya Saitou, E de Wakaru Jinrui no Shinka(Evolution of the Human Race which is Understood with Pictures), Koudan Sha, 2009. Illustrations: Saori Yasutomi

The New View

B.C. A.D.

The Jyomon Era Late period Final period

The Yayoi Era

The Jyomon Era

Final period

The Yayoi Era The Kofun Era

The Kofun Era

Late period

卑弥呼 Himiko

The Old View

Emergence of the People of the Japanese Islands:Three Hypotheses

• Replacement: Descendants of the first migrants were the original inhabitants, and descendants of a second wave, of a different lineage, are the modern Japanese.

• Mixing: Descendants of the first migrants interbred with later migrants to give rise to the modern Japanese.

• Continuity: Descendants of the first migrants changed over time and became the modern Japanese.

Three Major Hypotheses of the Emergence of the People of the Japanese Islands

• Replacement: von Siebold, Morse, Shogoro Tsuboi, Yoshikiyo Koganei, others

• Interbreeding: Erwin von Bälz, Ryozo Torii, Kenji Kiyono, Takeo Kanaseki, Bin Yamaguchi, Kazuro Hanihara, Kei‘ichi Omoto, Satoshi Horai, Katsushi Tokunaga, others • Continuity: Kotondo Hasebe, Hisashi Suzuki

Center/Periphery Theory

• Where a distribution is observed in the pattern ABA, the older are A words, the older B words tend to be. A = Ainu and Okinawans B = Main-island Japanese

Secular Change in Nasal Root Protrusion, Height and Cranial Index Suzuki, Hone kara Mita Nihonjin no Roots (The Roots of the Japanese as Seen in Their Bones) (1983)

Modern Japanese: • Tall stature * Y • High nose * J • Round head * J

‡ Hisashi Suzuki, Hone kara Mita Nihonjin no Roots (The Roots of the Japanese as Seen in Their Bones), Iwanami Shinsho, 1983

Fig VII-9 Secular change in Japanese traits

Century

Nasal root protrusion C

ranial index

Height Height

Cranial index

Protrusion of nasal root

Jyomon

protrusion

Yayoi Kofun Recent times

Today

Ancient times

The Middle times

アイヌ人縄文人

モンゴル人南部中国人

アラスカエスキモーアリュート

カナダエスキモー

土居が浜 ( 弥生 )J( 古墳 )J( 室町 ) J( 鎌倉 )金隈 ( 弥生 )

J( 現代 -南西日本 )

J( 現代 -東日本 )J( 江戸 )

オンタリオイロコワ族

Neighbor-Joining Tree of Japanese and Neighboring Populations According to Continuous Variation in Skulls Dodo, Ishida and Saitou (1992)

‡ Naruya Saitou, DNA kara Mita Nihonjin (The Japanese viewed from DNA), Chikuma Shinsho, 2005

Jomon people Ainu

Doigahama (Yayoi) J (Kofun)

J (modern, SW Japan) J (Edo)

J (modern, E Japan)

South Chinese

Alaskan Eskimos Aleuts

Canadian Eskimos

Ontario Iroquois

Mongolians J (Muromachi)

J(Kamakura) Kanenokuma (Yayoi)

Relatedness of Human Populations According to Continuous Variation in Morphology Hajime Ishida, et al (2006)

Jomon people

Main-island Japanese

Anthropological Science Vol. 114 (2006) , No. 2 pp.141-151 ”Nonmetric cranial variation of early modern human skeletal remains from Kumejima, Okinawa and the peopling of the Ryukyu Islands” Tadahiko Fukumine, Tsunehiko Hanihara, Akira Nishime, Hajime Ishida ‡

Emergence of the Japanese According to the Dual-Structure Model Hanihara, Nihonjin no Naritachi (Emergence of the Japanese), (1990)

‡

Kazuro Hanihara, Nihonjin no Naritachi (Emergence of the Japanese), Jimbun Shoin, 1990

Proto-Asians

Epi-Jomon people

Jomon people

NE Asians

NE Asia neolithic peoples

Fig 11-8 The process of emergence of the Japanese (Based on principal component analysis of craniometric values)

In-migrating groups (Yayoi to 8th century)

Mainland Japanese Okinawans Ainu

SW island Kofun people

Mutation

The Heart of Evolution: DNA accumulates mutations while undergoing repeated self-replication.

O遺伝子における１塩基の欠失 (X ) によって引き起こされたフレームシフト突然変異

塩基配列: 　　　 A AAGGATGTCCTCGTGGTGACCCCTTGGCTGGCTCCCATTGTCTGGGAGGGCACATTCAAC B G O X G タンパク質のアミノ酸配列: A/B K D V L V V T P W L A P I V W E G T F N O K D V L V V P L G W L P L S G R A H S T A転移酵素と B 転移酵素の酵素活性の違いを与えている２個のアミノ酸の違い(+)と、そ

れを引き起こすA遺伝子とB遺伝子２個の塩基の違い (!)

遺伝子の塩基配列 : A GATTTCTACTACCTGGGGGGGTTCTTCGGGGGGTCGGTGCAAGAG B A C ! ! 酵素タンパク質のアミノ酸配列 : A D F Y Y L G G F F G G S V Q R B D F Y Y M G A F F G G S V Q R + +

Frame-shift mutation caused by the deletion of one nucleotide (X) in the O gene

Nucleotide sequences:

Protein amino acid sequences:

The differences (+) in two amino acids conferring a difference in enzyme activity between transferase A and transferase B, and the differences(!) between two

nucleotides in gene A and gene B causing that to happen

Genetic nucleotide sequences:

Enzyme protein amino acid sequences:

Fumiichiro Yamamoto et al, Nature (1990)

SNP Single Nucleotide Polymorphism

‡

Common ancestral gene of humans and chimpanzees

Mutation

Now

Humans Chimpanzee

Time

Naruya Saitou, Genomu to Shinka – Genomu kara Tachinoboru Seimei (Genomes and Evolution – Life Ascendent from Genomes), Shin'yosha, 2004. Illustrations: Saori Yasutomi

SNP Single Nucleotide Polymorphism

‡ Illustrations: Saori Yasutomi

Naruya Saitou, Genomu to Shinka – Genomu kara Tachinoboru Seimei (Genomes and Evolution – Life Ascendent from Genomes), Shin'yosha, 2004.

Looking at nucleotide sequences in genes on homologous chromosomes . . .

Hetero-pair AG Homo-pair AA Homo-pair GG Hetero-pair AG

Fig 4-6 Single nucleotide polymorphism SNP (A Single-Nucleosome polymorphism) is a DNA sequence variation occurring when a single nucleotide in a genome. In the above figure, there are examples of each individuals, that is Homo-pair of G or A, and Herero-pair of A and G.

Individual Genetic Differences among Human Beings

0.07% = 0.07 x 0.01 x 3 billion x 2

= c.4.2 million nucleotide differences

Random Genetic Drift

Parent generation

Child generation

Eggs selection of genes Random

Sperm

Insemination

Computer Simulation of Random Genetic Drift (Saitou, Genomu Shinka-gaku Nyumon (Introduction to Genome Evolution)

‡

(A) 1,000 individuals

Gene frequency

Generations

(B) 10,000 individuals

Generations G

ene frequency

Naruya Saitou, Genomu Shinka Gaku Nyuumon(Introduction to Genome Evolution), Kyouritsu Shuppan, 2007.

ABO Blood Type Gene Frequency Japanese Koreans Chinese Indonesians

Dogrib Guayami Wapisiana Aymara

Yanomama Baniva Cayapo Maquiritare

Papuans Iranians Germans San

Genetic Neighbor-Joining Tree for 30 Populations Worldwide Saitou (1995)

‡

North Americans

Meganesians (Sahul)

Africans West Eurasians

East Eurasians

South Americans


Saitou N. (1995) A genetic affinity analysis of human populations. Human Evolution, Vol. 10, No. 1, pp. 17-33.

Neanderthals

Modern East Eurasians Modern Oceanians Modern West Eurasians Modern Africans

Genealogical tree of human mitochondrial DNA

A F212402（チュクチ人）


A F212401（チュクチ人）、A F212403（チュクチ人）、A Y 005526（バルカン半島人）

U 33368（モンゴル人）




A Y 005493（バルカン半島人）



A B 059887（ブリヤート人）、A F 273588（ウイグル人）、A F 273589（カザフ人）



A Y 024647（北欧人）

U 37745（香港人）

A Y 025878（北欧人）、A Y 025877（北欧人）

U 25380（パプアニューギニア人）

M 76312（ナイジェリア人）


U 37742（香港人）




A B 059877（ブリヤート人）、U 33373（モンゴル人）


U 25378（パプアニューギニア人）U 33383（モンゴル人）



A F249845（インド人）

A F273576（ウイグル人）、A F273577（カザフ人）、U 33393（モンゴル人）、A B 059873（ブリヤート人）


A F087014（インドネシア人）

A F249844（インド人）、A F249843（インド人）


A Y 025645（北欧人）

A Y 025300（北欧人）

A F273586（ウイグル人）

A B 059886（ブリヤート人）

M 76291（ナイジェリア人）




A F273572（ウイグル人）、U 33339（モンゴル人）、A B 059889（ブリヤート人）

A Y 025410（北欧人）

A Y 025070（北欧人）

A Y 025990（北欧人）

A Y 025999（北欧人）

A Y 025106（北欧人）

A Y 025670（北欧人）

A Y 025378（北欧人）

A Y 025228（英国人）

A Y 025298（英国人）

A Y 025500（北欧人）

A Y 024881（英国人）

M 76270（アフリカ系米国人）

M 76264（東部ピグミー人）

M 76235（西部ピグミー人）

M 76236（西部ピグミー人）

M 76237（アフリカ系米国人）

A F254446（ネアンデルタール人・南ロシア）

A F282971（ネアンデルタール人・クロアチア）

A F011222（ネアンデルタール人・ドイツ）

0.010

Genealogical tree of human mitochondrial DNA, 52 complete sequences

Africans


Africans West Eurasians East Eurasians Meganesians (Sahul) Americans

A genealogical chart of mtDNA in the entire world (Ingman et al., 2000)

Inferred Route of Human Diffusion from Africa Over Past 150,000 Years


Taiwan, the Philippines, Northeast China, Mongolia

Genetic Relatedness of Pacific Rim Populations (Omoto and Saitou, 1997)

‡ Naruya Saitou, DNA kara Mita Nihonjin (The Japanese viewed from DNA), Chikuma Shinsho, 2005 Omoto K. and Saitou N. (1997) Genetic origins of the Japanese: A partial support for the "dual structure hypothesis". American Journal of Physical Anthropology, Vol. 102, No. 4, pp. 437-446.

Native North Americans Eskimos

Native Australians Papua New Guineans

Koreans Mongolians Main-island Japanese

Tibetans Ainu

Okinawans South Chinese

Thais Filipinos

Negritos (Mamanwa) Indonesians

Polynesians Micronesians

Negritos (Aeta)

Native South Americans

1

2

3

4

5

6

‡

Migratory Routes to the Japanese Islands

DNA kara Mita Nihonjin

(The Japanese viewed from DNA)


日本人

モンゴル族１ホイ族

モンゴル族２カザフ族

モンゴル族３チベット族

韓国人漢族（北京）

漢族（徐州）

漢族（広州）漢族（広西）

ドン族チュアン族

ヤオ族

漢族（海南島）

ミヤオ族（海南島）

リー族（海南島）

北方の集団

南方の集団

Neighbor-Joining Tree for East Asian Populations with Focus on China, Based on HLA Data Tokunaga and Saitou (1988)

‡ Naruya Saitou, DNA kara Mita Nihonjin (The Japanese viewed from DNA), Chikuma Shinsho, 2005 Naruya Saitou, Katsushi Tokunaga (1998) HLA kougenkei kara Mita Nihonjin (The Japanese viewed from HLA), Iden (Heredity), Vol. 42, No. 10, pp. 40-46.

Mongolians 1

Kazakhs

Han (Xuzhou) Koreans Han (Beijing)

Northern populations Southern populations

Han (Guangxi) Han (Guangxu)

Dong Zhuang

Miao (Hainan) Yao

Han (Hainan)

Li (Hainan)

Japanese Hui

Mongolians 2

Mongolians 3 Tibetans

Genetic Relatedness Estimated from Data on 10 Genes, Including ABO Blood Type Saitou (1994)

‡ Naruya Saitou, DNA kara Mita Nihonjin (The Japanese viewed from DNA), Chikuma Shinsho, 2005 Saitou N., Omoto K., Du C., and Du R. (1994) Population genetic study in Hainan Island, China. II. Genetic affinity analyses. Anthropological Science, Vol. 102, No. 2, pp. 129-147.

Hainan populations

Hainan Miao 1

Hainan Hui Thais

Hainan Han Filipinos Malaysians

Koreans

East Asian populations

Negritos

Hainan Li 2

Hainan Miao 2

Mongolians Japanese

Ainu

Zhuang

Fukien Han

Hainan Li 1

Javanese

Genetic Relatedness among Four Populations in the Japanese Islands Area:

An Unrooted Genealogical Tree Omoto and Saitou (1997)

Ainu

Koreans

Japanese main

islands

Okinawans

Naruya Saitou, DNA kara Mita Nihonjin (The Japanese viewed from DNA), Chikuma Shinsho, 2005 Omoto K. and Saitou N. (1997) Genetic origins of the Japanese: A partial support for the "dual structure hypothesis". American Journal of Physical Anthropology, Vol. 102, No. 4, pp. 437-446.

‡

本土日本人

韓国人

沖縄人

アイヌ人

Genetic Relatedness among Four Populations in the Japanese Islands Area: A Genealogical Network Saitou (2008)

Ainu

Koreans

Japanese main islands

Okinawans

Saitou N. (2008) Genetic Relationships of Human Populations in and around the Japanese Archipelago. In Matsumura S., Forster P. and Renfrew C. (eds.), "Simulations, genetics and human prehistory", McDonald Institute Monographs, Cambridge, pp. 89-92.

‡

Your Genome Is . . .

You

Mother Father


You

Grandmother Grandfather Grandmother Grandfather

Mother Father


You

Your Genome is Your Ancestral Fitness


Mother Father

You


Mother Father

You

Your Genome is Your Ancestral Fitness

Y染色体ミトコンドリアＤＮＡ

Paternal grandfather

Mother Father Self

Maternal grandmother

Maternal grandfather

Paternal grandmother

Mitochondrial DNA Y chromosome

Mitochondrial DNA Is Matrilineal

5 generations ago

4 generations ago

3 generations ago

2 generations ago

1 generation ago

Current generation

Next generation

Human Mitochondrial DNA Genome

16,569 base pairs Circular double-strand DNA

Ribosomal RNA tRNA Cytochrome reductase NADH-Q reductase Cytochrome oxidase ATP synthase

Naruya Saitou, Genomu to Shinka – Genomu kara Tachinoboru Seimei (Genomes and Evolution – Life Ascendent from Genomes), Shin'yosha, 2004.

‡

Illustrations: Saori Yasutomi

Gene Genealogy

突然変異

★

4N generations ago (expected value)

Mutation

Common ancestral gene

Now

2N generations (expected value)

Nucleotide sequences compared (multiple alignment)

Y Chromosome Haplotypes Present Only in Japanese Islanders


Population

Buryats Nivkhi Japanese islanders (Ainu group) Japanese islanders (Honshu group) Japanese islanders (Kyushu group) Japanese islanders (Okinawa group) North Chinese Han South Chinese Han (Taiwan) Indigenous Taiwanese ("Takasago" mountain peoples)

Filipinos Thais Malaysians

Table 4-3 Gene frequency (%) in Y chromosome haplotypes among Asian populations, with a focus on the Japanese islands

* YAP+ haplotypes (those with the Alu insertion sequence), Tajima and Horai (2004)

Data from Katsushi Tokunaga et al.

Leukocyte Blood-Type HLA Data


Table 4-2 HLA haplotype frequencies compared Japanese

main islands Okinawans Ainu Buryats Chinese Manchurians Northern Han Koreans Chinese Koreans

Microevolution and Inter-relatedness among Populations in the Japanese Islands DNA kara Mita Nihonjin (The Japanese viewed from DNA)

‡

Okhotsk culture

Hokkaido (Ainu)

Okinawans

Japanese main islands

Korean peninsula Mainland China

Now


1,000 yrs ago 3,000 yrs ago 10,000 yrs ago

Entire human genome (3.2 billion nucleotides) ┃ ┣ーGenes and gene-related regions (1.2 billion nucleotides) ┃ ┣ーGenes (48 million nucleotides) <-- Just 1.5% of the whole ┃ ┗ーGene-related regions (1,152 million nucleotides) ┃ ┗ Regions between genes (2.0 billion nucleotides) ┣Dispersed repetitive sequences (1.4 billion nucleotides) ┃ ┣ーLong dispersed repetitive sequences LINE (640 million nucleotides) ┃ ┣ーShort dispersed repetitive sequences SINE (420 million nucleotides) ┃ ┗ーOther repetitive sequences SINE (340 million nucleotides) ┗Other intergenic regions (600 million nucleotides) ┣ーMicrosatellites (90 million nucleotides) ┗ーNon-microsatellites (510 million nucleotides)

‡ The International Chimpanzee Chromosome 22 Consortium [H.Watanabe, A.Fujiyama, M.Hattori, T. D.Taylor, A.Toyoda, Y.Kuroki, H.Noguchi, A.BenKahla, H.Lehrach, R.Sudbrak, M.Kube,S.Taenzer, P.Galgoczy, M.Platzer, M.Scharfe, G.Nordsiek, H.Blocker, I.Hellmann, P.Khaitovich, S.Paabo, R.Reinhardt, H.-J.Zheng,X.-L.Zhang, G.-F.Zhu, B.-F.Wang, G.Fu, S.-X.Ren9, G.-P.Zhao, Z.Chen, Y.-S.Lee, J.-E.Cheong, S.-H.Choi, K.-M.Wu, T.-T.Liu, K.-J.Hsiao, S.-F.Tsai, C.-G.Kim, S.Oota, T.Kitano, Y.Kohara, N.Saitou, H.-S.Park, S.-Y.Wang, M.-L.Yaspo, and Y.Sakaki] (2004) DNA sequence and comparative analysis of chimpanzee chromosome 22. Nature, vol. 429, No. 6990, pp. 382-388

Microsatellite DNA Polymorphism

A)

B)

C)

＝ CTG, etc.

Lee, Yamamoto, Katsumata, Saitou et al, 2006 Shi-Lin Li et al., Human Genetics vol.118, no.6, 695-707 (2006) ‡

Studies Exploring Genetic Diversity among Five Populations of Han Chinese (International project in joint research with the Chinese Academy of Sciences [Beijing Institute of Genomics/Institute of Genetics and Developmental Biology])

‡

Fukien province

Guangdong province Okinawa

Nagoya

Shanxi province

Hunan province

Beijing Bangkok (Thailand)

Yangon (Myanmar)

Britain

(Lee, Yamamoto, Saitou et al,2006; Human Genetics)

Estimate of Genetic Relatedness among Nine Asian Populations Resulting from Microsatellite DNA

Polymorphism

Shi-Lin Li et al., Human Genetics vol.118, no.6, 695-707 (2006) ‡

Relationships between Japanese Islanders and Other Populations

Yamaguchi, Kamatani et al (2008)

Inserted here was deleted according to copyright issues.

Yamaguchi et al. The American Journal of Human Genetics, Volume 83, Issue 4, pages 445-456 (2008)

Large-Scale SNP Analysis of Japanese Islanders


Inserted here was deleted

according to copyright issues.


Placement of Regional Residents (1) Yamaguchi, Kamatani et al (2008)





Placement of Regional Residents (2)




Interpreting SNP Analysis Results

Chinese cluster

Korean cluster?

Japanese main islands cluster

Ryukyus cluster

Tohoku population distribution

Mixed cluster A

Mixed cluster B

Mixed cluster C

？ Saitou N. (2009) New Horizon of Human Genome Study, Anthropological Science. Vol.117, No.1, pp. 1-9.

‡

Map of China

Later Han

Early Han Chin Warring States

Spring &Autumn Annals

Chou

Late Shang（Yin）

Early Shang

Hsia

Yangshao （Neolithic）

2000 yrs ago

3000 yrs ago

4000 yrs ago

Chinese Chronology

Lingshi

Yinxu(Anyang)

Central Plain

‡

Genetic Relatedness between Two Populations in Ancient China and Modern Humans (Wang, Saitou, Ueda at al, 2000)

Wang et al., Molecular Biology and Evolution 17:1396-1400 (2000) ‡

Modern Central Asians

Turkish Uighurs

Mountain Kirghiz Altai

Modern Europeans

Welsh

Finns Germans

Icelandic

Portuguese

KaKazakhszakhs

Mongolians

Main-island Japanese

Koreans Ainu

Okinawa

Lingshi, Shandong province (modern)

Plains Kirghiz

Modern East Asians

Lingshi, Shandong province (Western Han- Eastern Han)

Lingshi, Shandong province

)

Two Populations in Ancient China and Modern Populations Compared(Wang, Saitou, Ueda at al, 2000)

Wang et al., Molecular Biology and Evolution 17:1396-1400 (2000) ‡

1

3

6

1 4

9 1 1

1 2 1 7 1 8

1 6 1 3 1 0

1 9

5 4

7

8 2

1 5

０１２ - １ - ２

０

１

- １

Modern Europeans

Modern Central Asians

Modern East

2500 years ago

2000 years ago Now

Earwax Inheritance Patterns Asians exhibit high frequencies of both moist and dry earwax. Moist is the dominant form of earwax. A single gene determines whether an individual's earwax is moist or dry. The gene determining earwax type is on an autosomal chromosome.

auricle

outer ear

middle ear

Inner ear

semicircular canal

cochlear nerve

cochlea

vestibular nerve

auditory canal

auditory ossicle

Ear canal

myrinx

Population Differences in Earwax Allele Frequencies Omoto, Bunshi-jinruigaku to Nihonin no Kigen

‡ (Molecular Anthropology and the Origins of the Japanese) (1996)

Wet-type

dry-type

Japan Okinawa

African American

Choctaw

Navaho Papago

Quechua Kuna

Hainan

North China

Menggu Tungus

Korea

Aynu Aleutian Islands

Mayan

South China

White American

North American Indian

Nootka

Melanesia

Micronesia Taiwan

Shuw

Ampon

Aborigine

A Short History of Earwax-Type Studies

Buntaro Adachi

1930s: Buntaro Adachi (Kyoto Imperial University Faculty of Medicine) produces scientific studies of earwax types. 1960s: Ei Matsunaga (Sapporo Medical University/National Institute of Genetics) confirms inheritance patterns in earwax types. 2002: Tomita, Shinkawa et al (Nagasaki University) specify the position of the earwax-type gene in the human genome. 2006: Yoshiura, Shinkawa (Nagasaki University) et al identify the earwax-type gene. Ei Matsunaga

‡Photo provided by：National Institute of Genetics

How to Infer Where a Disease-Related Gene Is Located on a Chromosome (Genetic linkage analysis)

B 1 3

B 2 4

B 1 4

B 2 3

b 1 3 E

病気の原因遺伝子 b ともとの遺伝子

病気遺伝子に近い遺伝子 ( 1 , 2 )

病気遺伝子から遠い遺伝子 ( 3 , 4 )

A

B C D

Disease-causing gene b and original gene B

Genes (1 and 2) near the disease gen

Genes (3 and 4) distant from the disease gene

Mutation

Splice so that only the gene b-1 combination remains

A

B

C

D

Genes (3 and 4) distant from the disease gene

F

Splice

E

Disease-causing gene b and original gene B

Genes (1 and 2) near the disease gen

Chromosome number 16

16p11.2

16q12.1

Mapped region

D16S3093

D16S3080

Pedigree Analysis with a Microsatellite DNA Polymorphism

(Tomita et al. 2002, Lancet)

~ 7.42 cM



Tomita et al. The Lancet Volume 359, Issue 9322, Pages 2000-2002 (2002)

Yoshiura et al (2006) Reprinted by permission from Macmillan Publishers Ltd: A SNP in the ABCC11 gene is the determinant of human earwax type Nature Genetics 38, 324 - 330, copyright (2006)

‡

Dry (function-less) resulted from moist (functional) with modification of a single amino acid

Moist protein (glycine)

Dry protein (arginine)

No protein

Differences in the Function of ABCC11 Gene Product Are the Cause of the Differences in Earwax

Yoshiura et al (2006)

Yoshiura et al (2006)

Reprinted by permission from Macmillan Publishers Ltd: A SNP in the ABCC11 gene is the determinant of human earwax type Nature Genetics 38, 324 - 330, copyright (2006)

‡

Yoshiura et al., (2006)

Distribution of Earwax Alleles ●：Moist ○：Dry

Reprinted by permission from Macmillan Publishers Ltd: A SNP in the ABCC11 gene is the determinant of human earwax type Nature Genetics 38, 324 - 330, copyright (2006)

‡

A single-nucleotide polymorphism in the ABCC11 gene is the determinant of human earwax type Koh-ichiro Yoshiura1,2, Akira Kinoshita1,2, Takafumi Ishida3, Aya Ninokata3,Toshihisa Ishikawa4, Tadashi Kaname2,5, Makoto Bannai6, Katsushi Tokunaga6, Shunro Sonoda7, Ryoichi Komaki8, Makoto Ihara9, Vladimir A. Saenko10, Gabit K. Alipov11, Ichiro Sekine11, Kazuki Komatsu12, Haruo Takahashi12, Mitsuko Nakashima1,2,13, Nadiya Sosonkina1,2, Christophe K. Mapendano1,2, Mohsen Ghadami1,2, Masayo Nomura1,2,14, De-Sheng Liang2,15, Nobutomo Miwa1,2, Dae-Kwang Kim16, Ariuntuul Garidkhuu17, Nagato Natsume17, Tohru Ohta2,18, Hiroaki Tomita19, Mihoko Kikuchi20, Graciela Russomando21, Kenji Hirayama20; Minaka Ishibashi22, Aya Takahashi22, Naruya Saitou22, Jeffery C. Murray23, Susumu Saito24, Yusuke Nakamura24,25, & Norio Niikawa1,2

Nature Genetics (2006)

Ainu-Language Place Names in Hokkaido

• Sapporo • Wakkanai • Noboribetsu • Ebetsu • Monbetsu • Nakashibetsu

Ainu-Language Place Names in Tohoku

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Tomabechi

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Mabuchi

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“ Sanesashi, Sagamu country's little moor

was burning Ah thou whom I inquired of,

standing in the midst of the flames of the fire ”

-- Princess Oto-tachibana

Geographic Distribution of Indo-European Languages Source：http://upload.wikimedia.org/wikipedia/commons/3/33/Indo-European_Groups_World_Distribution.gif

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http://upload.wikimedia.org/wikipedia/commons/3/33/Indo-European_Groups_World_Distribution.gif�



Indo-European Language Family Tree Gray & Atkinson (2004)


Gaelic

Limba

Spanish French

Breton Welsh

Portuguese Brazilian Portuguese

Italian Catalan

Latvian Lithuanian

Sardinian

English

Slovene

Swedish Icelandic Danish

Dutch German

Macedonian Bulgar

Serbo-Croatian

Ukrainian Slovak Czech

Polish Russian

Afrikaans

Lausitz

Byelorussian

Romani Sinhala Marathi

Gujarati

Hindi

Banjar

Nepali Bengali

Cascara

Albanian Afghan

Persian

Dutch

Greek Armenian

Tocharian languages Hittite

Which Language or Lanugage Family is Closest to Japanese?

• Korean: Hakuseki Arai, Kurakichi Shiratori, Shiro Hattori, A. Vovin, Katsumi Matsumoto,

others • Ainu: Shiro Hattori, Biden Yasumoto, Katsumi Matsumoto, Takeshi Umehara, others • Koguryo (dead language): Lee Ki-moon, Shichiro Murayama, C. Beckwith, Yoshizo Itabashi, others • Altaic language family: Katsuji Fujioka, Kyosuke Kindaichi, R.A. Miller, S.A. Starostin, others • Austronesian language family: Izuru Shinmura, Hisanosuke Izui, Shichiro Murayama, Takao Kawamoto, others

チュルク語

日本語韓国語

満語ツングース語

？

モンゴル語

Comparison of Basic Lexical Terms in Five Altaic Proto-Languages

(Vovin, 2003) Japanese proto-language–Korean proto-language: Bone, hair, moon, fire, cloud, water, leg Japanese proto-language–Korean proto-language–Manchurian Tungusic proto-language: Water, leg Japanese proto-lanugage–Mongolian proto-language: Blood Korean proto-language–Manchurian Tungusic proto-language: Nose Turkic proto-language–Other proto-language: None

Japanese Korean

Manchurian

Tungusic

Mongolian Turkic

Linguistic lineage network of languages in the vicinity of the Japanese islands based on initial-consonant matching patterns in 100 basic lexical terms collected by Yasumoto and Honda (1978) From DNA kara Mita Nihonjin (The Japanese viewed from DNA)

○○○●●

○○●●○ ○○●●●

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Modern Tokyo dialect

Middle Korean

3

15

Modern Okinawan dialect


Nara-era Japanese

Modern Ainu

Quoted in Naruya Saitou, "Jinshu Yo Saraba" (A Farewell to Race), collected in Yasuko Takezawa, ed., Jinshu Gainen no Fuhensei wo Tou (Is Race a Universal Idea?) (Jinbun Shouin, 2005) In J.D. Salinger's Raise the Roofbeam High, Carpenters, Zooey says: "He said he even wished everybody in the world looked exactly alike. He said you'd keep thinking everybody you met was your wife or your mother or father, and people would always be throwing their arms around each other wherever they went, and it would look 'very nice'."

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Jinshu Yo Saraba, Minzoku Yo Saraba (A Farewell to Race, A Farewell to Ethnicity) (Saitou, Minzoku-gaku Kenkyuu: 1997)

"'Nihonjin' ga Kieru Toki" (When the "Japanese" Disappear) (Saitou, in DNA kara Mita Nihonjin [The Japanese viewed from DNA], 2005

Tairiku kara no Michi, Tairiku he no Yume (The Road the Continent, Dreams of the Continent) (Saitou, Gakushi Kaiho: 2006)

Source：http://chikyu-to-umi.com/n-con/N-con-gallery-2007rid-b1-1.html ‡

Work no.: B1-1

Location: Osaka prefecture

Designer: Rid

Affiliation: Osaka College of Art, Osaka University of Arts

Designer's comments: Marinites was originally one of the Seagull coalition of city-states that proclaimed their independence after forming the coalition of Pacific Ocean megafloat cities in 2129. The structure comprises a built-up area resting on half-submerged floats and an airport island constructed likewise and linked to it by bridge, as well as an atoll encircled with giant embankments to prevent submersion due to global warming. Originally constructed as a marine technologies research facility, Marinites hosts many technical research facilities, shipyards and other industrial plant. Residential units for their employees' families are attached to their workplaces and zoned accordingly. Inherent to the city are its large hydrogen plant and wave- and wind-power generators that even permit it to export energy. Unlike other megafloat cities, Marinites is linked to a natural island by bridge and so enjoys its own supply of natural foods to complement those produced in its factories and megafloats, making it completely self-sufficient. The city held fast to its neutrality during the Fourth Great War, when it took in large numbers of refugees. To accommodate these new residents, the city constructed new megafloats and embankments, enlarged its capacity and conducted maintenance works to achieve the configuration seen now in 2200.

Support Category

A Floating City-State: Marinites

http://chikyu-to-umi.com/n-con/N-con-gallery-2007rid-b1-1.html�

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The Japanese viewed from DNA,

by Naruya Saitou Chikuma Shinsho

Published March 2005

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Documents

What Our Genome Says about the Origins of the … Single Nucleotide Polymorphism ‡ Illustrations: Saori Yasutomi Naruya Saitou, Genomu to Shinka – Genomu kara Tachinoboru Seimei